Between 10 and 20 million American men are impotent. Several disease states such as atherosclerosis and diabetes mellitus have a high prevalence of impotence. Hypertension, hypercholesterolemia, diabetes mellitus and cigarette smoking are among the risk factors which may contribute to penile erectile dysfunction. It is now realized that the state of tone of human corpus cavernosum (HCC) smooth muscle plays a major role in the hemodynamics of penile erection. Previous research has focused exclusively on the neurologic control of HCC smooth muscle tone. Preliminary work indicates that the endothelium lining the lacunar spaces may influence HCC smooth muscle tone. The overall aim of this proposal is to determine the physiological role of the vascular endothelium in the control of HCC smooth muscle tone. HCC endothelial cells (EC) have, for the first time, been isolated, cultured and partially characterized. This proposal intends to establish an in vitro model system, utilizing HCC EC in culture, to investigate the interactions between the endothelium, smooth muscle and nerves of HCC. It is proposed: a) To continue the characterization of HCC EC and HCC smooth muscle cells in culture. b) To investigate the stimuli (mechanical or chemical) which cause the release of prostaglandins (PGs) from HCC EC, and to determine if these PGs have a role in the control of HCC smooth muscle tone, either directly or by inhibition of adrenergic neurotransmission. c) To determine if HCC EC release endothelium derived relaxing factor (EDRF) in response to mechanical or chemical stimuli. d) To determine if HCC EC synthesize and release acetylcholine. The outcome of this work may establish, for the first time, the physiological role of the vascular endothelium in penile erection. It will also allow the recognition of specific pathophysiological mechanisms leading to impotence in systemic diseases, such as diabetes mellitus and atherosclerosis, affecting normal EC function.